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The hypothalamic\u2013pituitary\u2013adrenocortical (HPA) axis regulating cortisol release has been extensively studied; however, attempts to target the HPA axis pharmacologically to treat major depression have failed. This review focuses on the importance of the adrenocortical stress hormone aldosterone, which is released by adrenocorticotropic hormone and angiotensin, and the mineralocorticoid receptor (MR) in depression. Depressed patients, in particular those with atypical depression, have signs of central hyperactivation of the aldosterone sensitive MR, potentially as a consequence of a reactive aldosterone release induced by low blood pressure and as a result of low sensitivity of peripheral MR. This is reflected in reduced heart rate variability, increased salt appetite and sleep changes in this group of patients. In addition, enlarged brain ventricles, compressed corpus callosum and changes of the choroid plexus are associated with increased aldosterone (in relation to cortisol). Furthermore, subjects with these features often show obesity. These characteristics are related to a worse antidepressant treatment outcome. Alterations in choroid plexus function as a consequence of increased aldosterone levels, autonomic dysregulation, metabolic changes and\/or inflammation may be involved. The characterization of this regulatory system is in its early days but may identify new targets for therapeutic interventions.<\/jats:p>","DOI":"10.1111\/jne.13219","type":"journal-article","created":{"date-parts":[[2022,11,20]],"date-time":"2022-11-20T08:09:57Z","timestamp":1668931797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A viewpoint on aldosterone and\n                    <scp>BMI<\/scp>\n                    related brain morphology in relation to treatment outcome in patients with major depression"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4827-1945","authenticated-orcid":false,"given":"Harald","family":"Murck","sequence":"first","affiliation":[{"name":"Philipps\u2010University Marburg Marburg Germany"},{"name":"Murck\u2010Neuroscience LLC Westfield Westfield NJ 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